Choline is an essential nutrient that a lot of us don’t get enough of. In fact, the majority of the US population doesn’t get enough choline on a daily basis. Insufficient choline can impact mental sharpness, heart health, fatty liver disease, and more. [ref]
This article digs into the research on the various different forms of choline and how genetic variants impact our need for choline. Genetics play a big role in how well your body creates and uses choline.
Why do we need choline?
Choline is involved in several critical roles in the body including:
- supporting methylation reactions through donating a methyl group
- formation of acetylcholine, a neurotransmitter and cell-signaling molecule
- formation of phosphatidylcholine which makes up cell membranes[ref]
- muscle function [ref]
- deficiency in choline contributes to non-alcoholic fatty liver disease[ref]
Recent studies of choline show:
- Academic achievement in 15-year olds is significantly associated with plasma choline levels[ref] Wow – I have a hard time wrapping my head around the idea that a nutrient can be that important for academic achievement.
- Choline plus B-vitamins may increase neuroplasticity and speed recovery after a stroke [ref]
- Choline deficiency is correlated to lower bone mineral density [ref]
Making choline in the body vs. choline from food:
Generally, people can make some choline in their liver. This is not enough choline to meet all the needs of the body, though, so it is essential to also get choline via the diet. Additionally, some people have genetic variants that reduce their ability to make choline, thus increasing their need for choline from food.
The FDA recommends an adequate intake for adults of 425-550 mg/day for choline. [ref]
Acetylcholine – an important neurotransmitter:
Choline is the precursor to acetylcholine, which is an important neurotransmitter. Acetylcholine is the signaling molecule for neurons that control muscles, heart rhythm, and other functions.
Choline in the methylation cycle:
Your body’s need for choline from the diet will depend in part on how much folate you eat and how well your methylation cycle works. Choline acts as a methyl donor in the methylation cycle, and with low folate or decreased enzyme efficiency in the folate pathways, your choline requirement may increase.
Specifically, choline in the form of betaine (also known as trimethylglycine) acts as a methyl donor within the methylation cycle.[ref]
When choline levels are low, homocysteine levels can increase, which is associated with an increased risk of cardiovascular disease. Increasing levels of betaine in the diet are linked with lower homocysteine levels. [ref]
A study published in the American Journal of Clinical Nutrition found that with just two weeks of supplemental choline (2.6 g/day as phosphatidylcholine), homocysteine levels dropped by 18% compared to placebo.[ref]
Choline for the brain:
Choline is a precursor for acetylcholine, a neurotransmitter involved in learning and memory. Acetylcholine is essential for healthy cognitive function. Simply put, we need choline to think and function well. [ref]
In a mouse model of Alzheimer’s disease, giving the mice choline for most of their life reduced the Alzheimer’s pathology. [ref] Yes – this is just a mouse study. But the cholinergic system is important in Alzheimer’s disease, and commonly used medications for Alzheimer’s include acetylcholinesterase inhibitors.
Fatty liver disease and choline deficiency:
A study of 57 normal adults investigated the effects of limiting either choline from the diet or folate from the diet for a period of 6-weeks. The study found that 77% of postmenopausal women and 80% of men developed fatty liver disease in the six weeks of choline deprivations (<50mg/day). No significant changes were found from limiting folate in the diet. [ref]
Choline requirements in pregnancy:
Choline is an essential component of cell membranes, so a developing fetus needs a lot of choline. Women who are pregnant or nursing thus have a greater need for choline. When pregnant, a woman will produce more choline, which is then transported to the developing baby. So despite the increased production of choline, pregnant women end up low in choline. Breast milk is also high in choline, so nursing the baby also depletes the mother of choline. [ref]
Genetic variants that impact choline:
The PEMT gene codes for the enzyme phosphatidylethanolamine N-methyltransferase. Also, the PEMT pathway is responsible for the body’s production of phosphatidylcholine, which is part of the phospholipid bilayer making up the membranes surrounding our cells. The PEMT enzyme is key in the body’s ability to create choline. Genetic variants that decrease the function of the enzyme cause greater reliance on choline from dietary sources.
Check your genetic data for rs7946 V175M (23andMe v4, v5; AncestryDNA)
- C/C: typical PEMT activity (most common genotype worldwide)
- C/T: somewhat decreased PEMT enzyme activity
- T/T: decreased PEMT enzyme activity [ref] increased risk of non-alcoholic fatty liver disease in lean people[ref][ref] ( most common genotype for Caucasian populations)
Members: Your genotype for rs7946 is —.
Check your genetic data for rs12325817 (AncestryDNA)
- C/C: typical
- C/G: increased risk of organ dysfunction with low choline diet
- G/G: significantly increased risk of organ dysfunction with low choline diet[ref]
Members: Your genotype for rs12325817 is —.
The CHKA gene codes for the choline kinase alpha enzyme, which is involved in the pathway of reactions that converts choline into phosphatidylcholine (needed for cell membranes). Choline kinase specifically is the catalyst in the reaction that converts choline into O-phosphocholine. The variant below decreases the turnover of dietary methionine into choline. Carriers of the variant are more likely to need dietary choline since they don’t convert dietary protein (methionine) into choline very well.
Check your genetic data for rs10791957 (23andMe v4, v5; AncestryDNA)
- A/A: reduced turnover of methionine to phosphatidylcholine [ref] [ref]
- A/C: reduced turnover of methionine to phosphatidylcholine
- C/C: typical
Members: Your genotype for rs10791957 is —.
The BHMT gene codes for the Betaine-homocysteine S-methyltransferase enzyme. This enzyme is used in the conversion of homocysteine using a methyl group from choline (betaine).
Check your genetic data for rs3733890 (23andMe v4, v5; AncestryDNA):
- A/A: decreased conversion of choline to betaine (needed as a methyl donor) and more conversion of choline to CDP-PC [ref][ref] folate treatment less likely to reduce homocysteine[ref]
- A/G: decreased conversion of choline to betaine and more conversion of choline to CDP-PC
- G/G: typical
Members: Your genotype for rs3733890 is —.
FMO3 – Flavin-containing monooxygenase
The FMO3 gene codes for the flanvin-containing monooxygenase 3 enzyme, which is important liver enzyme for breaking down a number of substances.It is important in the conversion of TMAO, a substance that is implicated in atherosclerosis.
Check your genetic data for rs2266782 (23andMe v4, v5):
- A/A: a greater turnover of betaine to methionine and a greater turnover of choline-derived methionine to PEMT-PC in women[ref]
- A/G: a greater turnover of betaine to methionine and a greater turnover of choline-derived methionine to PEMT-PC in women
- G/G: typical
Members: Your genotype for rs2266782 is —.
The MTHFD1 gene codes for the enzyme called methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1. This is actually an enzyme in the folate pathway, but it affects your need for adequate choline in the diet.
Check your genetic data for rs2236225 (G1958A): (23andMe v4, v5; AncestryDNA)
- A/A: decreased MTHFD1 enzyme stability[ref] more of a reliance on choline as a methyl donor [ref] [ref]
- A/G: decreased MTHFD1 enzyme stability[ref] more of a reliance on choline as a methyl donor
- G/G: typical
Members: Your genotype for rs2236225 is —.
Carriers of the A allele are more likely to have choline deficiency on a low choline diet (modified by folate intake) [ref] [ref] In one study with premenopausal women, those with an A-allele were 15 times more likely to show choline deficiency symptoms on a diet low in choline.
Excellent (egg-cellent :-) sources of choline in foods include: eggs, liver, shitake mushrooms, milk, and various meats.[ref]
|Beef liver, pan-fried, 3 ounces||356||65|
|Egg, hard-boiled, 1 large egg||147||27|
|Beef top round, separable lean only, braised, 3 ounces||117||21|
|Soybeans, roasted, ½ cup||107||19|
|Chicken breast, roasted, 3 ounces||72||13|
|Beef, ground, 93% lean meat, broiled, 3 ounces||72||13|
|Fish, cod, Atlantic, cooked, dry heat, 3 ounces||71||13|
|Mushrooms, shiitake, cooked, ½ cup pieces||58||11|
|Potatoes, red, baked, flesh and skin, 1 large potato||57||10|
|Wheat germ, toasted, 1 ounce||51||9|
|Beans, kidney, canned, ½ cup||45||8|
|Quinoa, cooked, 1 cup||43||8|
|Milk, 1% fat, 1 cup||43||8|
|Yogurt, vanilla, nonfat, 1 cup||38||7|
Meat and eggs are the most abundant sources of choline — but even so, a serving of chicken breast gives you 13% of the recommended daily value.
In short, if you want to know how much choline you normally get in your diet, you should track what you eat for a week or so. The free online app, cronometer.com, includes the choline content of foods. Choline content isn’t enabled by default, so you will need to go into the settings and turn on ‘choline’.
There are several options for choline if you are looking to optimize your cognition and mental clarity. It is one of the basic brain-building blocks and the basis for acetylcholine. Raw choline donors help with brain energy.
Choline supplement options include CDP-choline, phosphatidylcholine, alpha-GPC, and choline citrate. Examine.com is a good source of information on the different types of choline.
- Choline bitartrate – simple and cheap source of choline, but not all that effective at crossing the blood-brain barrier in people.
- Alpha GCP – can cross the blood-brain barrier. Alleviates impaired memory.
- CDP Choline – both choline plus uridine precursor.
More to read: Linus Pauling Institute (University of Oregon) – Choline
Related Genes and Topics:
One very important gene that has been very well researched for Alzheimer’s disease is the APOE gene. This gene is involved in carrying cholesterol and other fats in your bloodstream, and a common variant of the gene is linked to a higher risk of Alzheimer’s. Late-onset Alzheimer’s disease (after age 60) is thought to be influenced both by genes and by environmental factors, so keep in mind when looking at your genetic risk that your genes are only one part of the equation when it comes to Alzheimer’s (and many other diseases!). Knowing your risk can help you to understand the importance of doing all that you can to prevent Alzheimer’s disease.
It is easy to check your genetic results on 23andMe or AncestryDNA for the two main MTHFR variants known as C677T and A1298C. If you have 23andMe results (it doesn’t matter if you have the health option or not!), click on the link below to check your MTHFR gene. If you have AncestryDNA results, you will need to download your raw data file and search for the rs id number below.
Originally published 5/2017. Updated 1/2020.